Changes In Microvasculature Research Articles

Dimension-based quantification of aging-associated cerebral microvasculature determined by optical coherence tomography and two-photon microscopy.

Cerebral microvascular health is a key biomarker for the study of natural aging and associated neurological diseases. Our aim is to quantify aging-associated change of microvasculature at diverse dimensions in mice brain. We used optical coherence tomography (OCT) and two-photon microscopy (TPM) to obtain nonaged and aged C57BL/6J mice cerebral microvascular images in vivo. Our results indicated that artery & vein, arteriole & venule, and capillary from nonaged and aged mice showed significant differences in density, diameter, complexity, perimeter, and tortuosity. OCT angiography and TPM provided the comprehensive quantification for arteriole and venule via compensating the limitation of each modality alone. We further demonstrated that arteriole and venule at specific dimensions exhibited negative correlations in most quantification analyses between nonaged and aged mice, which indicated that TPM and OCT were able to offer complementary vascular information to study the change of cerebral blood vessels in aging.

Retinal microcirculation alterations in rheumatoid arthritis patients compared to healty volunteers and their correlation to the disease activity and duration of disease

Aims/Purpose: Patients with rheumatoid arthritis (RA) have a high risk of developing cardiovascular diseases due to endothelial dysfunction, which is a risk factor for cardiovascular events. The retinal Vessel Analyzer (RVA, IMEDOS Systems) can capture retinal vessels non‐invasively in real‐time and analyse their dynamic responses to stimuli.Methods: In order to assess the structural and functional changes in the retinal microvasculature, a non‐invasive Retinal Vessels Analyzer (RVA) was used to study 44 patients with RA (mean age 57.4 ± 13.2 years) and compare them to a control group of 44 age‐matched healthy individuals. The RVA was used to measure various parameters, including the Central Retinal Artery Equivalent (CRAE), Central Retinal Vein Equivalent (CRVE), and Arterio‐Venous Ratio (AVR), as well as the response of the retinal vessels to flickering light. After a 50 s baseline, rectangular shape, monochromatic flickering light (530–600 nm) of 12.5 Hz for 20 s was applied three times. The dilation of retinal vessels after flicker light stimulation was analysed.Results: The results of the study showed that patients with RA had significantly higher CRVE and lower AVR compared to the control group (p = 0.04 and p = 0.01, respectively), indicating structural changes in the retinal microvasculature. The patients with RA also had a significantly stronger arterial dilation response to flickering light compared to the control group (n = 43), indicating functional changes in the retinal microvasculature. In patients with moderate to high disease activity according to the Disease Activity Score (DAS‐28 > 3.2) (n = 9), there was a negative significant correlation between the maximum arterial diameter (aMAX) and interleukin‐6 (IL‐6).Conclusions: These findings suggest that RVA can be a useful tool for detecting structural and functional changes in the retinal microvasculature of patients with RA and that the disease activity and inflammation in RA may be related to these changes. However, the study notes that a larger cohort with a wider range of disease activity is needed to fully understand the effect of chronic inflammatory diseases on endothelial function.

DEVELOPMENT AND APPLICATION OF R1RHO DISPERSION IMAGING OF AGING MUSCLE IN AN ANIMAL MODEL

Abstract Compelling evidence from animal studies demonstrates that microvascular impairment contributes to the etiologies of several age-related chronic diseases, including sarcopenia. For example, capillary hemodynamic profiles are altered in old F344 rat spinotrapezius muscle compared with those of younger counterparts. However, a validated non-invasive measure of microvasculature geometry and structure has not yet been developed. Recently, it has been shown that R1ρ dispersion imaging at weak locking field frequencies (FSL) provides a unique way of characterizing microvessel size and density. Moreover, previous R1ρ images were acquired at strong FSL (≥500Hz) and used to measure the age-related differences linked to macromolecular deposition, such as collagen in the extracellular matrix. Here, we aimed to develop a non-invasive 3D volume R1ρ dispersion imaging method at weak FSLs (< 300Hz), to quantify microvasculature changes in skeletal muscle. We successfully implemented the protocol and applied it to the lower leg of five F334 female rats at age 15 mo. The whole lower leg of each rat was also imaged using conventional multislice T1-FLASH, Diffusion-weighted, and T2-MGE pulse sequences. We found that R1p value measured in calf muscles decreased from 46.92Hz to 41.63Hz by increasing FSL from 5Hz to 240Hz, which we suggest derives from the effects of rephasing some of the signal losses that arise from diffusion in intrinsic magnetic field gradients generated from microvessels. Future direction of this ongoing study will be to compare these results with data collected from young female rats at age 6 months and further validation using ex-vivo histology.

Characterization of retinal microvasculature and structure in atrial fibrillation.

Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF). This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion. A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (β coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (β coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; β coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (β coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05). This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

Multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence imaging of USH2A knockout rabbits

Usher syndrome type 2A (USH2A) is a genetic disorder characterized by retinal degeneration and hearing loss. To better understand the pathogenesis and progression of this syndrome, animal models such as USH2A knockout (USH2AKO) rabbits have been developed. In this study, we employed multimodal imaging techniques, including photoacoustic microscopy (PAM), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA) imaging to evaluate the retinal changes in the USH2AKO rabbit model. Twelve New Zealand White rabbits including USH2AKO and wild type (WT) were used for the experiments. Multimodal imaging was implemented at different time points over a period of 12 months to visualize the progression of retinal changes in USH2AKO rabbits. The results demonstrate that ellipsoid zone (EZ) disruption and degeneration, key features of Usher syndrome, began at the age of 4 months old and persisted up to 12 months. The EZ degeneration areas were clearly observed on the FAF and OCT images. The FAF images revealed retinal pigment epithelium (RPE) degeneration, confirming the presence of the disease phenotype in the USH2AKO rabbits. In addition, PAM images provided high-resolution and high image contrast of the optic nerve and the retinal microvasculature, including retinal vessels, choroidal vessels, and capillaries in three-dimensions. The quantification of EZ fluorescent intensity using FAF and EZ thickness using OCT provided comprehensive quantitative data on the progression of degenerative changes over time. This multimodal imaging approach allowed for a comprehensive and non-invasive assessment of retinal structure, microvasculature, and degenerative changes in the USH2AKO rabbit model. The combination of PAM, OCT, and fluorescent imaging facilitated longitudinal monitoring of disease progression and provided valuable insights into the pathophysiology of USH2A syndrome. These findings contribute to the understanding of USH2A syndrome and may have implications for the development of diagnostic and therapeutic strategies for affected individuals. The multimodal imaging techniques employed in this study offer a promising platform for preclinical evaluation of potential treatments and may pave the way for future clinical applications in patients with Usher syndrome.

Multimodal retinal imaging in individuals with frontotemporal dementia compared to controls

AbstractBackgroundA growing body of literature has shown a relationship between neurodegenerative diseases and ocular changes. Frontotemporal dementia (FTD) affects individuals under age 65. We use optical coherence tomography (OCT) and OCT angiography (OCTA) to characterize the retinal microvasculature and retinal and choroidal structure in patients with FTD vs normal cognition.MethodCross‐sectional comparison of patients with FTD to age‐ and sex‐matched controls with normal cognition. Exclusion criteria included diabetes, glaucoma, uncontrolled hypertension, and retinal or optic nerve pathology. Participants underwent OCT and OCTA imaging using the Zeiss Cirrus HD‐5000 Spectral‐Domain OCT with AngioPlex. Primary outcome measures included OCT parameters: subfoveal choroidal thickness, central subfield thickness, ganglion cell layer‐inner plexiform layer (GC‐IPL) thickness, and retinal nerve fiber layer (RNFL) thickness; and OCTA parameters: superficial capillary plexus foveal avascular zone area, 3×3mm and 6×6mm macular vessel density (VD) and perfusion density (PD), and 4.5×4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equations accounting for correlation between 2 eyes of the same subject were utilized for statistical analysis.ResultTwenty‐eight eyes of 17 participants with FTD and 85 eyes of 48 patients with normal cognition were analyzed. Individuals with FTD were matched to their normal cognition counterparts with regard to sex (64.7% vs 62.5% men, p = 0.871) and age (67.82 vs 68.98 years, p = 0.958). Compared to normal cognition participants, MMSE scores of FTD participants were significantly lower (p &lt; 0.001). In FTD, average 4.5×4.5‐mm CFI was decreased compared to controls (p = 0.032). There was no difference in average 4.5×4.5mm CPD between FTD and controls (p = 0.172).ConclusionIndividuals with FTD exhibited significantly reduced average CFI compared to controls. Retinal microvasculature changes may be useful as a biomarker for FTD diagnosis.

Retinal microvasculature and risk of incident dementia over a 10‐year period: results from the 3C‐Alienor population‐based study

AbstractBackgroundThe retina and the brain microvasculatures share many anatomical and physiological similarities; thus, retinal microvasculature could represent a potential screening tool for cerebrovascular and neurodegenerative diseases. Changes in retinal microvasculature have been associated with dementia in previous studies. However, all the previous studies analyzing retinal vascular network features in relation to dementia or Alzheimer Disease (AD) were cross‐sectional. This study aimed to explore the longitudinal relationship between retinal microvascular features and dementia incidence over a 10‐year follow‐up period.MethodWe included 617 participants from the Three‐City (3C) population‐based cohort and its ancillary ophthalmological study, the Alienor study. Quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were assessed at baseline in the Alienor study using the semi‐automated Singapore I Vessel Assessment (SIVA) software; dementia was actively screened and diagnosed over a 10‐year period. Cox proportional‐hazards models were used to estimate the risk of incident dementia and its main etiologies (i.e., probable or possible AD and mixed or vascular dementia) associated with retinal vascular features.ResultThe mean age of the participants was 79.5 years (SD 4.4) and 66.6% were women. During the follow‐up (median of 7.2 years), 134 participants developed dementia (87 probable or possible AD and 38 mixed or vascular dementia). In multivariate models adjusted for the main potential confounders (socio‐demographic factors, vascular co‐morbidities and Apolipoprotein ε4 allele), increased arteriolar tortuosity was associated with increased risk of dementia (HR per SD increase = 1.26, 95%CI: 1.07; 1.50). Despite some trends, retinal calibers were not significantly associated with dementia all‐cause. When considering the different etiologies of dementia, wider retinal venular calibers were associated with mixed or vascular dementia, but not with Alzheimer’s disease. Fractal dimensions were not associated with dementia.ConclusionChanges in retinal microvasculature were associated with risk of incident dementia. More works are needed to replicate and determine which features could help identifying persons at risk of future dementia at an early stage, and to examine the specific processes that might be involved according to dementia etiology.

Insight into the Brain: Application of the Retinal Microvasculature as a Biomarker for Cerebrovascular Diseases through Optical Coherence Tomography Angiography.

The present article serves as a comprehensive review of the published research literature surrounding the retinal microvasculature, characterized through the optical coherence tomography angiography (OCTA) and its potential clinical value for understanding and detecting cerebrovascular diseases. Studies from the past 3 years (2020-2023) have identified a degeneration of the retinal microvasculature, commonly defined through the loss of vascular density, in ischemic stroke, dementia, carotid artery stenosis, cerebral small vessel disease, and a series of rare, potentially inherited cerebrovascular disorders. These retinal microvascular changes often correlate with structure and functional changes in the brain and sometimes occur prior to debilitating neurodegeneration. While further investigations with longitudinal data and larger sample sizes are necessary, OCTA shows promising results for characterizing the retinal microvasculature as a potential imaging biomarker in reflecting the changes in the cerebral microvasculature for early detection, prevention, and treatment of cerebrovascular diseases.

Associations between microstructural tissue changes, white matter hyperintensity severity, and cognitive impairment: an intravoxel incoherent motion imaging study

IntroductionWhite matter hyperintensities (WMHs) are a common age- and vascular risk factor-related disease and have been recognized to play an important role in cognitive impairment. However, it is still unclear what the mechanism of this effect is. In this study, intravoxel incoherent motion (IVIM) was employed to assess the microvasculature and parenchymal microstructure changes of WMHs and explore their relationship with cognitive function.MethodsForty-nine WMH patients and thirty-one healthy controls underwent IVIM imaging, a diffusion technique that provides parenchymal diffusivity D, intravascular diffusivity D*, and perfusion fraction f . The IVIM dual exponential model parameters were obtained in specific regions of interest, including deep white matter hyperintensities (DWMHs), periventricular white matter hyperintensities (PWMHs), and normal-appearing white matter (NAWM). The independent-sample t-test or Mann–Whitney U-test was utilized to compare IVIM parameters between patients and controls. The Kruskal–Wallis test or one-way analysis of variance was used to compare IVIM parameters among DWMH, PWMH, and NAWM for patients. The Wilcoxon two-sample test or independent-sample t-test was used to assess the differences in IVIM parameters based on the severity of WMH. The multivariate linear regression analysis was conducted to explore the factors influencing cognitive scores.ResultsWMH patients exhibited significantly higher parenchymal diffusivity D than controls in DWMH, PWMH, and NAWM (all p &amp;lt; 0.05). IVIM parameters in the three groups (DWMH, PWMH, and NAWM) were significantly different for patients (all p &amp;lt; 0.001). The severe WMH group had a significantly higher parenchymal diffusivity D (DWMH and PWMH) than mild WMH (both p &amp;lt; 0.05). The multiple linear regression analysis identified D in DWMH and PWMH as influencing cognitive function scores (all p &amp;lt; 0.05).ConclusionIVIM has the potential to provide a quantitative marker of parenchymal diffusivity for assessing the severity of WMH and may serve as a quantitative marker of cognitive dysfunction in WMH patients.

Optical Coherence Tomography Angiography Changes in Macular Area in Patients with Proliferative Diabetic Retinopathy Treated with Panretinal Photocoagulation.

The purpose of this study was to investigate the changes in macular microvasculature using optical coherence tomography angiography (OCTA) in association with functional changes in patients with proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) with a follow up of 12 months. The participants in this study were 28 patients with PDR and no macular oedema, who were eligible for PRP. All participants underwent best-corrected visual acuity (BCVA) measurement, optical coherence tomography (OCT), and OCT angiography (OCTA) at baseline (before treatment) and at months 1, 6, and 12 after the completion of PRP treatment. The comparison of OCTA parameters and BCVA between baseline and months 1, 6, and 12 after PRP was performed. There was a statistically significant decrease in foveal avascular zone (FAZ) area at months 6 and 12 of the follow-up period compared to baseline (p = 0.014 and p = 0.011 for month 6 and 12, respectively). Of note is that FAZ became significantly more circular 6 months after PRP (p = 0.009), and remained so at month 12 (p = 0.015). There was a significant increase in the mean foveal and parafoveal vessel density (VD) at all quadrants at the superficial capillary plexus (SCP) at month 6 and month 12 after PRP compared to baseline. No difference was noticed in VD at the deep capillary plexus (DCP) at any time-point of the follow up. BCVA remained the same throughout the follow-up period. At months 6 and 12 after PRP, foveal and parafoveal VD at SCP significantly increased compared to baseline, while the FAZ area significantly decreased and FAZ became more circular.

Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study

PurposeThe aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. MethodsHealthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. ResultsA total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). ConclusionsExcessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Changes in Macular Thickness and Microvasculature in Koreans with Early Parkinson’s Disease

Purpose: To investigate the thickness of the nerve fiber layer-ganglion cell inner plexiform layer (NFL-GCIPL) complex and microvascular macular changes in Korean patients with early Parkinson’s disease using optical coherence tomography (OCT) and OCT angiography (OCTA).Methods: Forty-three eyes of 22 patients with early Parkinson’s disease were included. A control group of 20 patients (40 eyes) was also recruited. The thickness of the NFL-GCIPL macular complex was measured using OCT, and the densities of the superficial and deep macular retinal vessels were evaluated via OCTA in all subjects.Results: The NFL-GCIPL thicknesses of the superior, inferior, temporal, and nasal sectors were 94.70 ± 9.35, 93.32 ± 9.16, 90.18 ± 6.32, and 93.11 ± 8.75 μm in the control group and 92.05 ± 4.96, 91.32 ± 7.48, 84.74 ± 6.82, and 91.32 ± 7.47 μm in the Parkinson’s disease group, respectively; all thicknesses were significantly greater in the control group. The superficial and deep retinal vessel densities did not differ between the two groups.Conclusions: Neurodegenerative macular changes are more obvious than microvascular changes in patients with early Parkinson’s disease. Such neurodegenerative changes should be further evaluated in future cohort studies.

Changes in peripapillary microvasculature in patients with type 2 diabetes patients: effect of systemic hypertension

To determine the effect of hypertension (HTN) on the peripapillary microvasculature in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). The patients were classified into three groups: the control group (group 1), T2DM group (group 2), and both T2DM and HTN group (group 3). Peripapillary vessel density (VD) was compared using analysis of covariance and linear regression analysis was performed to identify the factors affecting the peripapillary VD. A total of 286 eyes were enrolled: 124 in group 1, 111 in group 2, and 51 in group 3. The peripapillary VDs for the full area were 18.3 ± 0.6, 17.8 ± 1.0, and 17.3 ± 1.2 mm−1 in group 1, group 2, and group 3, respectively, which were significantly different after adjustment for age and best-corrected visual acuity (P < 0.001). In post hoc analyses, group 1 versus group 2 (P < 0.001), group 1 versus group 3 (P < 0.001), and group 2 versus group 3 (P = 0.001) showed significant differences. In linear regression analysis, HTN (B = − 0.352, P = 0.043) and peripapillary retinal nerve fiber layer (pRNFL) thickness (B = 0.045, P < 0.001) were significantly associated with peripapillary VD in T2DM patients. Peripapillary VD in T2DM patients without clinical DR were lower compared to normal controls, and they were more decreased when HTN was comorbid. The combination of ischemic damage by high blood pressure and impairment of the neurovascular unit by hyperglycemia would result in more severe deterioration of peripapillary microvasculature, and this impairment could be also reflected by pRNFL thinning.

The value of indocyanine green-FLOW800 in microvasculature for predicting cerebral hyperperfusion syndrome in moyamoya disease patients

Among the notable complications of direct hemodynamic reconstruction for moyamoya disease (MMD) is cerebral hyperperfusion syndrome (CHS). In this study, we evaluated hemodynamic changes in small regional microvasculature (SRMV) around the anastomosis site by using indocyanine green (ICG)-FLOW800 video angiography and verified that it better predicted the onset of CHS. Intraoperative ICG-FLOW800 analysis was performed on 31 patients (36 cerebral hemispheres) with MMD who underwent superficial temporal artery-middle cerebral artery (MCA) bypass grafting at our institution. The regions of interest were established in the SRMV and thicker MCA around the anastomosis. Calculations were made for half-peak to time (TTP1/2), cerebral blood volume (CBV), and cerebral blood flow (CBF). According to the presence or absence of CHS after surgery, CHS and non-CHS groups of patients were separated. The results showed that ΔCBV and ΔCBF were substantially greater in SRMV than in MCA (p < 0.001). Compared with the non-CHS group, ΔCBF and ΔCBV of SRMV and MCA were considerably greater in the CHS group (p < 0.001). ΔCBF and ΔCBV on the ROC curve for both SRMV and MCA had high sensitivity and specificity (SRMV: ΔCBF, AUC = 0.8586; ΔCBV, AUC = 0.8158. MCA: ΔCBF, AUC = 0.7993; ΔCBV, AUC = 0.8684). ICG-FLOW800 video angiography verified the differential hemodynamic changes in the peri-anastomotic MCA and SRMV before and after bypass surgery in patients with MMD.

Analyses of the ratio of ganglion cell-inner plexiform layer thickness to vessel density according to age in healthy eyes.

To identify how the inner retinal layer and microvasculature change with age by analyzing the relationships of ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD), and the ratio of these measurements with age in healthy eyes. Participants were divided into five groups according to age. The GC-IPL thickness, VD, and GC-IPL/VD ratio were compared among the groups. Linear regression analyses were performed to identify relationships of GC-IPL/VD ratio with age. The average GC-IPL thicknesses were 84.84 ± 5.28, 84.22 ± 5.30, 85.20 ± 6.29, 83.29 ± 7.06, and 82.26 ± 5.62 μm in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The VDs were 20.94 ± 1.50, 21.06 ± 1.50, 20.99 ± 1.03, 20.71 ± 0.93, and 19.74 ± 1.73 mm-1 in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The GC-IPL/VD ratio was 4.05, 4.00, 4.06, 4.02, and 4.17 in each group, respectively, and the ratio of the 60s age group was significantly higher than that of other groups. In linear regression analyses, the GC-IPL/VD ratio was significantly associated with age in the participants aged ≥ 50 years (B = 0.014, P = 0.013), whereas it was not in the participants aged < 50 years (B = 0.003, P = 0.434). GC-IPL thickness and macular VD showed a tendency to decrease beginning in the 50s age group and the GC-IPL/VD ratio was significantly increased in the 60s age group. Additionally, the GC-IPL/VD ratio was positively associated with age in subjects aged ≥ 50 years, which implies a more pronounced decline over time in VD rather than GC-IPL thickness.

Perifoveal Microvascular Changes following Internal Limiting Membrane Peeling Surgery for Epiretinal Membrane and Macular Hole

Introduction: The aim of the study was to evaluate perifoveal microvasculature changes following pars plana vitrectomy with internal limiting membrane peeling for the epiretinal membrane (ERM) and macular hole (MH). Methods: This retrospective study included 59 eyes from 59 patients. Subjects were divided into two groups: an ERM group (n = 43) and an MH group (n = 16) based on the initial diagnosis. Swept-source optical coherence tomography angiography (SS-OCTA) was performed in the macular area, pre- and postoperatively. Perifoveal microvascular changes were calculated using MATLAB from the 6 × 6 mm SS-OCTA images, excluding the foveal avascular zone. Pre- and postoperative perifoveal vessel densities (pfVDs) were separately analyzed in six sectors (superior, superotemporal, inferotemporal, inferior, inferonasal, and superonasal) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The baseline characteristics and other clinical factors were compared between the ERM and MH groups. Results: The postoperative best-corrected visual acuity significantly improved in both groups (p < 0.05). One year after surgery, the pfVD in the SCP of the ERM group significantly decreased in the inferotemporal sector (p = 0.049). The postoperative pfVD in the DCP of the MH group significantly decreased in temporal sectors (p < 0.05). The postoperative mean pfVD in the SCP in the MH group was significantly lower than that in the ERM group (p = 0.003). The presence of a dissociated optic nerve fiber layer (DONFL) was 75% in the MH group and 22% in the ERM group (p = 0.018). The correlation between the pfVD and DONFL was not statistically significant. Conclusion: Postoperative pfVD reduction in the temporal sector, a corresponding area in which DONFL is present after MH surgery, was significantly observed. After vitreoretinal surgery in MH patients, OCTA may serve as a useful tool for monitoring perifoveal microvascular changes, especially in temporal sectors.

Opening a window to skin biomarkers for diabetes stage with optoacoustic mesoscopy

Being the largest and most accessible organ of the human body, the skin could offer a window to diabetes-related complications on the microvasculature. However, skin microvasculature is typically assessed by histological analysis, which is not suited for applications to large populations or longitudinal studies. We introduce ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need for contrast agents. Providing unique imaging contrast, we explored a possible role for RSOM as an investigational tool in diabetes healthcare and offer the first comprehensive study investigating the relationship between different diabetes complications and microvascular features in vivo. We applied RSOM to scan the pretibial area of 95 participants with diabetes mellitus and 48 age-matched volunteers without diabetes, grouped according to disease complications, and extracted six label-free optoacoustic biomarkers of human skin, including dermal microvasculature density and epidermal parameters, based on a novel image-processing pipeline. We then correlated these biomarkers to disease severity and found statistically significant effects on microvasculature parameters as a function of diabetes complications. We discuss how label-free RSOM biomarkers can lead to a quantitative assessment of the systemic effects of diabetes and its complications, complementing the qualitative assessment allowed by current clinical metrics, possibly leading to a precise scoring system that captures the gradual evolution of the disease.

Sex Variations in Retinal Microcirculation Response to Lower Body Negative Pressure.

Lower body negative pressure (LBNP) is routinely used to induce central hypovolemia. LBNP leads to a shift in blood to the lower extremities. While the effects of LBNP on physiological responses and large arteries have been widely reported, there is almost no literature regarding how these cephalad fluid shifts affect the microvasculature. The present study evaluated the changes in retinal microcirculation parameters induced by LBNP in both males and females. Forty-four participants were recruited for the present study. The retinal measurements were performed at six time points during the LBNP protocol. To prevent the development of cardiovascular collapse (syncope) in the healthy participants, graded LBNP until a maximum of -40 mmHg was applied. A non-mydriatic, hand-held Optomed Aurora retinal camera was used to capture the retinal images. MONA Reva software (version 2.1.1) was used to analyze the central retinal arterial and venous diameter changes during the LBNP application. Repeated measures ANOVAs, including sex as the between-subjects factor and the grade of the LBNP as the within-subjects factor, were performed. No significant changes in retinal microcirculation were observed between the evaluated time points or across the sexes. Graded LBNP application did not lead to changes in the retinal microvasculature across the sexes. The present study is the first in the given area that attempted to capture the changes in retinal microcirculation caused by central hypovolemia during LBNP. However, further research is needed with higher LBNP levels, including those that can induce pre-fainting (presyncope), to fully understand how retinal microcirculation adapts during complete cardiovascular collapse (e.g., during hypovolemic shock) and/or during severe hemorrhage.

Investigation of OCTA Biomarkers in Fabry Disease: A Long Term Follow-Up of Macular Vessel Area Density and Foveal Avascular Zone Metrics.

Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Prospective study of 26 eyes with FD followed up to 48months (mean 24, range 8-48). OCT angiography (OCTA) images (2.9 × 2.9mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = - 0.6; p < 0.0001). This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.

Short-term effects of occlusion therapy and optical correction on microvasculature in monocular amblyopia: a retrospective case–control study

This retrospective longitudinal case–control study investigated the short-term effects of patch occlusion treatment compared with optical correction on the microvasculature in monocular amblyopia. We included patients with monocular amblyopia treated for 2–12 months; they were classified into two groups according to the treatment regimen: patch occlusion or optical correction. Children aged < 12 years who presented to our clinic for examination without amblyopia diagnosis were enrolled as the control group. Changes in retinal and choroid microvasculature according to treatment were examined, and the correlation between changes in microvasculature and improvement in best-corrected visual acuity (BCVA) was evaluated. There were 57, 35, and 41 patients in the patch occlusion, optical correction, and control groups, respectively (mean age, 6.4 ± 2.0 years). Both amblyopic groups showed changes in the foveal and parafoveal deep capillary plexus vessel density (DCPD), choroidal thickness, and choroidal vascularity index (CVI) following short-term treatment (mean, 4.5 months). In the patch occlusion group, BCVA improved as the foveal DCPD increased (P = 0.013) and the CVI decreased (P = 0.037). In the optical correction group, BCVA improved as the foveal and parafoveal DCPD increased (P = 0.009). Increased foveal DCPD following amblyopia treatment and decreased CVI by patch occlusion were associated with improved BCVA.